The reference in this specification to any prior art publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
Controlled adhesion and cohesion of powders, including actions such as compression, compaction, densification, powder deposition, coating, adhesion or sintering are very common steps in the manufacture of solid powder forms of many functional or active agents such as pharmaceuticals, nutraceuticals, cosmetics, foods, detergents, inks, dyes, agricultural products and veterinary products. In each of the above, compatibility, compression, segregation, dispersion, adhesion, friction and flow are key factors, and depend on the surface properties, shape, deformation (including plasticity and elasticity), density, electrostatic (and other electronic) factors of the particles in the powder.
Compacts of solid dry powder forms are typically made by compressing a powder of particulate solid between two punches in a die of a compact press and subsequent ejection from the die. For the ingredients to be transformed into compacts of satisfactory quality, the formulation must have the key attributes of suitable flow, fluidity and compressibility. More specifically the powders to be compressed or compacted desirably have the following attributes:                Flow: the powder particles must flow into the die space of the press sufficiently rapidly and in a reproducible manner. The weight of the compact, and hence the dosage of active or functional agent, is dependent upon the volume of material which fills the die and unless the material flows freely into the die, unacceptable variation in compact weight, homogeneity in structure and content may ensue;        Cohesion: the particles must cohere when subjected to a compressing force, and that coherence should remain after the compressive force has been removed, otherwise after compression the compact will crumble and fall apart on handling; and        Lubrication: after the compression event is complete, it must be possible for the compact to be removed freely from the press without damage to either the compact or the press.        
Very few powdered functional or active ingredients possess all of these attributes in their original state, and indeed many possess none. Thus these materials generally require significant processing and subjection to treatments with other additive materials, such as diluents or fillers; binders (which are used to bind the powders together); disintegrants (which help the compacts to break up and dissolve); glidants (which are used to improve granule flow); anti-adherents or lubricants (which help the release of the compressed compact from the die); and anti-adhesives (which are sometimes used to prevent film residue being left on the die/punch) in order to achieve powders with the desired characteristics for solid form manufacture.
One method of addressing this is the process of granulation, or size enlargement, which is often required in order to achieve the necessary characteristics of flow and subsequent compression into tablet forms that adhere together in a structure that is strong enough to undergo subsequent processing, storage and ultimate handling and delivery.
In wet granulation, the process generally involves addition of several excipients in substantial quantities, and the use of a liquid (typically water) to aid the formation of a granule, often including a binder in solution. Not only does the complexity of this process make it costly (in terms of the number of steps, time, of equipment, of energy consumption, of materials), the addition of water to an active or functional agent which is moisture-sensitive increases the risk of decomposition. Furthermore, heat is then required to dry the granules, again with risk of decomposition of the active or functional agent.
In dry granulation, although water is avoided, the process also generally involves addition of several excipients in substantial quantities. The mixture is blended and then passed through a partial compaction process to form a ribbon, which is then milled into suitable granules. Again, the complexity of this process makes it costly, in terms of the number of steps, time, equipment, energy, and materials.
In these processes, the excipients often need to be added in significant quantities to allow the tablet ingredients to compact and bind together effectively on compression. The resulting tablets are often notably large, especially where high doses of the active or functional agent are required to be delivered, and for pharmaceutical dosage forms intended for oral administration, such large tablets may present patients with swallowing difficulties.
Tablet-like forms may also be made by a hot-melt extrusion, whereby the active agent is contained within a deformable polymer which can be extruded, such as polyvinylpyrrolidone (PVP). However, again this requires a significant mass of polymer, and the process requires the use of heat which may be disadvantageous.
Direct compression of the component powders can potentially overcome some of the disadvantages associated with granulation processes, as only prior blending of powders is required. However, in practice, the component powders (e.g. active agent, filler or carrier, binders, lubricants etc) often vary in size, shape, density and degree of cohesiveness, and typically an interactive mixture is obtained, wherein the cohesive particles adhere to free-flowing particles. Again, often only a very low level of active agent can be incorporated. Further, using known binder powders, the flow of such small sized powders is usually very poor, as these are too cohesive to blend efficiently to the other powders of the formulation in order to fill the compact dye with sufficient consistency.
In each of these cases, the powder composition and structure needs to be such that during compression, significantly strong bonding is formed between the particles. The formation of such bonds under compression follows a process of plastic and elastic deformation and/or fracture, which must then form these strong bonds between the particles to ensure that the tablets are sufficiently strong to avoid breakage or other faults during production, handling, transport and storage.
There are few real alternatives to these approaches currently used, despite the fact that substantial limitations exist in all cases, and that solid pharmaceutical oral dosage forms are by far the most common form of medication. Additives and/or processes which allow for improvements in both the product form as well as simplification of the manufacturing process, are therefore highly desirable.